"Pure" hepatoid tumors of the pancreas harboring CTNNB1 somatic mutations: a new entity among solid pseudopapillary neoplasms

Abstract

Hepatoid tumors (HTs) represent a rare group of neoplasms that are histologically similar to hepatocellular carcinoma but arise outside the liver. The current World Health Organization classification recognizes the hepatoid morphology of pancreatic tumors only as a possible variant of pancreatic ductal adenocarcinoma (PDAC). Here, we describe two cases of "pure" HT of the pancreas showing common features and characterized by indolent biological behavior. These tumors were roundish nodules with pushing borders, hyaline globules, and pure hepatoid histology; they were diffusely positive for β-catenin and LEF1 on immunohistochemistry. At next-generation sequencing, both neoplasms harbored only one pathogenic somatic mutation that affected the CTNNB1 gene at exon 3 and showed a loss of heterozygosity on chromosomes 18 and 21. By integrating macroscopic and microscopic features, along with their molecular profiles, we advocate that such tumors represent a distinct entity from PDAC and should be considered a new variant of solid pseudopapillary neoplasms. The recognition of this new neoplastic category may have immediate implications not only for tumor taxonomy but also for clinical practice.

Keywords: CTNNB1; Hep Par-1; Hepatoid; PDAC; Pancreas; Pancreatic; Pancreatic ductal adenocarcinoma; Solid pseudopapillary.

Fig. 1

Macroscopic image of case #2. Tumor mass was located in the pancreatic tail and appeared as a round yellow-brownish nodule, with pushing borders. Also case #1 had the same features, but arose in the pancreatic head

Fig. 2

Highly illustrative microscopic images of the described cases: A low-magnification image showing tumor pushing borders and the thickened tumor capsule (hematoxylin–eosin, 4 × original magnification; tumor capsule is indicated with a black asterisk); B both tumors show the focal presence of hyaline globules (hematoxylin–eosin, 20 × original magnification); C some areas with “steatohepatitis-like” appearance are also present (hematoxylin–eosin, 10 × original magnification); D foci of foamy macrophages are encountered (black arrow; hematoxylin–eosin, 10 × original magnification); E, F beta-catenin nuclear positivity in both cases (E 20 × , F 10 × original magnification; in F, the normal pancreatic parenchyma with normal membranous staining pattern is indicated with a black asterisk); G Hep Par-1 demonstrated a strong and diffuse staining pattern (10 × original magnification); H CD10 demonstrated a strong staining pattern, with a typical canalicular enhancement (10 × original magnification)